Celldex’s Barzolvolimab Hits Phase 3 Endpoints in Chronic Spontaneous Urticaria

Celldex reported positive Phase 3 results for barzolvolimab in chronic spontaneous urticaria (CSU), with both EMBARQ-CSU1 (NCT06445023) and EMBARQ-CSU2 (NCT06455202) meeting their primary and key secondary endpoints. The treatment produced sustained improvements in urticaria activity and complete disease response through 24 weeks, including in patients with omalizumab-refractory disease.

Phase 3 Trials Show Significant Reduction in Disease Activity

The randomized, double-blind, placebo-controlled EMBARQ-CSU1 and EMBARQ-CSU2 trials enrolled 1,939 adults with CSU whose symptoms remained inadequately controlled despite H1-antihistamine treatment. The studies randomized 963 patients in CSU1 and 976 in CSU2 to barzolvolimab or placebo.

Patients received either 150 mg of barzolvolimab every four weeks (Q4W), following a 300 mg loading dose, or 300 mg every eight weeks (Q8W), following a 450 mg loading dose. Placebo-treated patients remained on placebo through Week 24, after which they were re-randomized to active barzolvolimab treatment. Treatment continues through Week 52.

At Week 12, both barzolvolimab regimens significantly reduced the weekly urticaria activity score (UAS7), the primary endpoint. In EMBARQ-CSU1, least-squares mean UAS7 changes were -20.2 with 150 mg Q4W and -20.5 with 300 mg Q8W, compared with -10.7 for placebo. In CSU2, the corresponding reductions were -20.2 and -19.7 versus -11.4 with placebo. All comparisons achieved p<0.00001.

Complete Response Rates Continued to Improve

The treatment effect extended beyond reductions in symptom scores. Complete response, defined as UAS7=0, occurred in 42.4% and 42.1% of patients receiving the 150 mg and 300 mg regimens, respectively, in CSU1 at Week 12. In CSU2, the rates were 45.7% and 44.0%, compared with 9.3% and 12.6% with placebo.

Responses increased further by Week 24. Complete response reached 49.0% and 45.1% in CSU1 and 54.0% and 48.4% in CSU2 for the two dosing regimens, respectively. The data indicate that clinical benefit was sustained or deepened between Weeks 12 and 24.

The benefit also extended to patients with disease refractory to omalizumab. At Week 12, complete response rates ranged from 41.7% to 55.3% across the active treatment groups, compared with 9.3% to 15.1% with placebo.

Angioedema Outcomes Add Further Clinical Evidence

Among patients with baseline angioedema, significantly more barzolvolimab-treated patients achieved complete resolution of angioedema, defined as AAS7=0. Rates at Week 12 ranged from 62.7% to 66.3% in CSU1 and 66.2% to 74.3% in CSU2, compared with approximately 34% with placebo in both studies.

Barzolvolimab is a humanized monoclonal antibody that targets the KIT receptor on mast cells. By binding a specific region of KIT and inhibiting its activity, the drug targets mast cells that contribute to hypersensitivity, allergic inflammation and chronic urticaria.

Safety Remains Favorable Through 24 Weeks

Celldex reported that barzolvolimab was well tolerated through the 24-week placebo-controlled period, with a safety profile consistent with previous Phase 2 experience.

However, the Phase 3 studies are continuing through Week 52, so longer-term safety data are still being collected. The current topline results therefore provide an assessment of safety through 24 weeks rather than the full 52-week treatment period.

Phase 3 Program Continues Toward 2027 Filing

Both EMBARQ studies remain ongoing, with treatment continuing through Week 52. At Week 24, patients initially assigned to placebo were re-randomized to active barzolvolimab treatment. Patients completing the trials can also enter a global Phase 3b long-term extension study.

Celldex plans to present detailed Phase 3 data at an upcoming medical meeting and expects to submit a Biologics License Application to the FDA in 2027.

The results strengthen the clinical development case for barzolvolimab in antihistamine-refractory CSU, including patients with severe disease, angioedema or inadequate response to omalizumab. Longer-term follow-up will provide additional evidence on durability of response and safety as the program advances toward regulatory submission.

Reference

Celldex Announces Positive Results from Phase 3 EMBARQ-CSU1 and EMBARQ-CSU2 Studies of Barzolvolimab Which Met Primary and All Key Secondary Endpoints, CellDex, 22 September 2026

A Phase 3 Study of Barzolvolimab in Participants with Chronic Spontaneous Urticaria (EMBARQ-CSU1), ClinicalTrials.gov ID NCT06445023

A Phase 3 Study of Barzolvolimab in Participants with Chronic Spontaneous Urticaria (CSU) (EMBARQ-CSU2), ClinicalTrials.gov ID NCT06455202